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Peptide methionine sulfoxide reductase (MsrA) is a virulence determinant in Mycoplasma genitalium
S Dhandayuthapani1, M W Blaylock, C M Bebear
1Department of Microbiology, The University of Texas Health Science Center at San Antonio, 78229, USA.
Abstract:
Mycoplasma genitalium is the smallest self-replicating microorganism and is implicated in human diseases, including urogenital and respiratory infections and arthritides. M. genitalium colonizes host cells primarily through adherence mechanisms mediated by a network of surface-associated membrane proteins, including adhesins and cytadherence-related proteins. In this paper, we show that cytadherence in M. genitalium is affected by an unrelated protein known as peptide methionine sulfoxide reductase (MsrA), an antioxidant repair enzyme that catalyzes the reduction of methionine sulfoxide [Met(O)] residues in proteins to methionine. An msrA disruption mutant of M. genitalium, constructed through homologous recombination, displayed markedly reduced adherence to sheep erythrocytes. In addition, the msrA mutant was incapable of growing in hamsters and exhibited hypersensitivity to hydrogen peroxide when compared to wild-type virulent M. genitalium. These results indicate that MsrA plays an important role in M. genitalium pathogenicity, possibly by protecting mycoplasma protein structures from oxidative damage or through alternate virulence-related pathways.
Insights
Mycoplasma genitalium adherence and pathogenicity are significantly impacted by the antioxidant enzyme peptide methionine sulfoxide reductase (MsrA). Disrupting MsrA reduces M. genitalium
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Mycoplasma genitalium is a minimal bacterium linked to human urogenital and respiratory infections.
- M. genitalium adheres to host cells via surface proteins, crucial for colonization.
- Oxidative stress is a factor in microbial pathogenesis.
Purpose of the Study:
- To investigate the role of peptide methionine sulfoxide reductase (MsrA) in M. genitalium adherence and pathogenicity.
- To characterize an M. genitalium msrA mutant's adherence, growth, and oxidative stress response.
Main Methods:
- Construction of an msrA disruption mutant using homologous recombination.
- Assessment of sheep erythrocyte adherence.
- In vivo growth studies in hamsters.
- Hydrogen peroxide sensitivity assays.
Main Results:
- The msrA mutant exhibited significantly reduced adherence to sheep erythrocytes.
- M. genitalium msrA mutant was unable to establish infection in hamsters.
- The mutant displayed increased sensitivity to hydrogen peroxide compared to wild-type.
Conclusions:
- MsrA is critical for M. genitalium adherence and pathogenicity.
- MsrA likely protects mycoplasma proteins from oxidative damage, contributing to virulence.
- MsrA may also be involved in other virulence-related pathways.